Ontology highlight
ABSTRACT:
PROVIDER: PRJNA543699 | ENA |
REPOSITORIES: ENA
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Project description:Oxygen fluctuation during tissue remodeling imposes a major metabolic challenge in human tumors. Stem-like tumor cells in glioblastomas are believed to possess extraordinary metabolic flexibility, enabling them to initiate growth even under non-permissive conditions. To identify adaptive response mechanism, we compared the effects of acute and chronic hypoxia versus oxygenation on stem-like glioblastoma (GS) cells. GS cell lines were established and propagated either under normoxia (21% O2) or hypoxia (1% O2) and subsequently exposed to acute normoxia or hypoxia, respectively. Gene expression profiling revealed that acute hypoxia predominantly induced metabolic pathways and cell cycle arrest, whereas chronic hypoxia activated neurodevelopmental processes. In particular, we found increased expression of glycolytic enzymes, especially of the preparatory phase of glycolysis, under acute hypoxia, whereas pentose phosphate pathway (PPP) enzymes were downregulated. The opposite was found for acute oxygenation of hypoxic GS cells. Findings were confirmed by qPCR and immunoblot analyses. Despite downregulation by hypoxia, expression of PPP enzymes is increased in GBMs compared to normal brain, whereas expression of hypoxia-inducible enzymes of the parallel preparatory phase of glycolysis is decreased. Immunohistochemistry revealed strong staining for PPP enzymes in the bulk of GBM tissue, especially in highly proliferative areas, but not in pseudopalisading (hypoxic) cells. Glycolytic enzymes displayed an inverse pattern. Mass spectrometric analysis using [1,2-13C2]-D-glucose showed reduced glucose flux through the PPP under hypoxia in favor of flux through glycolysis. Acute and chronic hypoxia increased cell migration but reduced proliferation, whereas normoxia had opposite effects. Our findings extend Warburg’s observations by showing that in most tumor cells the PPP, which supplies metabolites for biomass production, is favored over the parallel preparatory phase of glycolysis, but is suppressed under acute severe hypoxia, causing a switch to direct glycolysis to protect against hypoxic stress.
2020-12-31 | GSE45117 | GEO
Project description:Liver RNA-seq of fish under acute hypoxia
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Project description:This work aims to characterize cycling hypoxia induced changes in metabolism related genes expression in pancreatic cancer cell line. PANC1were exposed to either 7 hours cycles of hypoxia every other day for 20 cycles cyclic acute hypoxia, or to 72 hours cycles of hypoxia once a week for 5 cycles cyclic chronic hypoxia. Gene expression changes were profiled using RT PCR and compared to cells under normoxia. Western blotting analysis confirmed upregulation of hypoxia inducible factor 1 α, glucose 6 phosphate isomerase gene, and ribokinase gene. Genes encoding glycolysis enzymes were upregulated under cyclic acute more than chronic hypoxia including hexokinase2 and phosphoglycerate kinase1. Genes encoding pentose phosphate pathway enzymes transketolase and transaldolase were upregulated similarly. Genes encoding pyruvate dehydrogenases that block pyruvate flow to TCA cycle were significantly upregulated. Exposure of PANC1 cells to acute hypoxia results in upregulation of genes that shift cells metabolism toward glycolysis and pentose phosphate pathways in adaptation to hypoxic stress
2022-06-28 | GSE207065 | GEO